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  • Title: Meiotic and mitotic nondisjunction: lessons from preimplantation genetic diagnosis.
    Author: Kuliev A, Verlinsky Y.
    Journal: Hum Reprod Update; 2004; 10(5):401-7. PubMed ID: 15319376.
    Abstract:
    Direct testing of the outcome of the first and second meiotic divisions has become possible with the introduction of preimplantation genetic diagnosis (PGD) for aneuploidies. Testing of oocytes by fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies showed that more than half of oocytes from the IVF patients aged 35 years and older had chromosomal abnormalities, which originated from errors in meiosis I or meiosis II, or both: 41.9% of oocytes were aneuploid after meiosis I and 37.3% aneuploid after meiosis II, with 29.1% of these oocytes having both meiosis I and meiosis II errors. As a result, one third of oocytes detected as normal after meiosis I contained the meiosis II errors, and two thirds of those with meiosis II errors were already abnormal following meiosis I. Although the rates of chromosomal abnormalities deriving from meiosis I and II were comparable, meiosis I errors predominantly resulted in extra chromosome (chromatid) material in oocytes, in contrast to a random distribution of extra and missing chromatids after meiosis II. The majority of meiosis I abnormalities were represented by chromatid errors, which seem to be the major source of chromosomal abnormalities in the resulting embryos. Approximately one third of aneuploid oocytes deriving from sequential errors in the first and second meiotic divisions resulted in a balanced karyotype, representing a possible phenomenon of "aneuploidy rescue" during the second meiotic division. However, the majority of the embryos resulting from such oocytes appeared to be abnormal for the same or different chromosome(s), or were mosaic, suggesting a possible predisposition of the resulting embryos to further mitotic errors. Although the origin of a high frequency of mosaicism at the cleavage stage is not sufficiently understood, the mosaic embryos may originate from the chromosomally abnormal oocytes, as a result of a "trisomy rescue" mechanism during the first mitotic divisions, which renders polar body FISH analysis to have important clinical value for reliable pre-selection of aneuploidy-free embryos for transfer.
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